Serological Assessment for Celiac Disease in IgA Deficient Adults

Ning Wang,Bengt A Andersson,Charlotte Dahle,Jonas F Ludvigsson,Johan Rönnelid,Lennart Hammarström,Lucia Mincheva-Nilsson,Kerstin Elvin,Lennart Truedsson,Annica Lindkvist

doi:10.1371/journal.pone.0093180

Abstract

PurposeSelective immunoglobulin A deficiency is the most common primary immunodeficiency disorder that is strongly overrepresented among patients with celiac disease (CD). IgG antibodies against tissue transglutaminase (tTG) and deamidated gliadin peptides (DGP) serve as serological markers for CD in IgA deficient individuals, although the diagnostic value remains uncertain. The aim of this study was to investigate the prevalence of these markers in a large cohort of IgA deficient adults with confirmed or suspected CD and relate the findings to gluten free diet.MethodsSera from 488,156 individuals were screened for CD in seven Swedish clinical immunology laboratories between 1998 and 2012. In total, 356 out of 1,414 identified IgA deficient adults agreed to participate in this study and were resampled. Forty-seven IgA deficient blood donors served as controls. Analyses of IgG antibodies against tTG and DGP as well as HLA typing were performed and a questionnaire was used to investigate adherence to gluten free diet. Available biopsy results were collected.ResultsOut of the 356 IgA deficient resampled adults, 67 (18.8%) were positive for IgG anti-tTG and 79 (22.2%) for IgG anti-DGP, 54 had biopsy confirmed CD. Among the 47 IgA deficient blood donors, 4 (9%) were positive for IgG anti-tTG and 8 (17%) for anti-DGP. Four were diagnosed with biopsy verified CD, however, 2 of the patients were negative for all markers. Sixty-eight of 69 individuals with positive IgG anti-tTG were HLA-DQ2/DQ8 positive whereas 7 (18.9%) of the 37 individuals positive for IgG anti-DGP alone were not.ConclusionsIgG anti-tTG seems to be a more reliable marker for CD in IgA deficient adults whereas the diagnostic specificity of anti-DGP appears to be lower. High levels of IgG antibodies against tTG and DGP were frequently found in IgA deficient adults despite adhering to gluten free diet.

Highlights

Selective immunoglobulin A (IgA) deficiency is the most common primary immunodeficiency in Caucasians with a frequency of 1/600 in the general population
IgA deficiency has been reported to be strongly associated with the B8-DR3-DQ2 haplotype [12,13], which is the strongest recognized risk haplotype for celiac disease (CD) as well
Anti-tissue transglutaminase (tTG) antibodies, 56 (15.7%) for IgG anti-deamidated gliadin peptides (DGP) with the INOVA assay and 76 (21.3%) with the Euroimmun assay

Summary

Introduction

Selective immunoglobulin A (IgA) deficiency is the most common primary immunodeficiency in Caucasians with a frequency of 1/600 in the general population. Two-thirds individuals with IgA deficiency are clinically asymptomatic, but the defect may be associated with recurrent respiratory and gastrointestinal tract infections and selected autoimmune disorders [2]. In studies on small cohorts, IgA deficient patients have been shown to have a 10 to 20-fold increased risk of developing CD [9–. CD is associated with another IgA deficiency associated haplotype, DR7-DQ2, albeit to a much lesser degree [14,15]. Taken together, this might explain the overlap between CD and IgA deficiency, indicative of a common genetic background

Objectives

Methods

Results

Discussion

Conclusion